Fish oil, misuse & inflammatory disease - Rob Wolf

Ahhh…fish oil. A whole industry built around supplying us with something that should be a natural part of our food supply. Prior to the 1970’s meat and dairy in the United states was still grass fed so we received ample amounts of the main constituents of fish oil, EPA and DHA, as part of our normal diet. With the adoption of grain feeding our cattle and the use of seed and vegetable oils heavy in the short omega 6 fat (linoleic acid) we have witnessed a dramatic shift away from the essential fatty acid profile we’d expect to see from an ancestral diet of ~1-1 or 2-1 N-6/N-3 to more than 10-1.

The health implications of this shift have not been great. The N-6 family tends to produce “pro-inflammatory” cellular signaling, while the N-3 family tends to produce “anti-inflammatory” signaling. This is a simplification but it get’s the idea across. More accurately, with excessive N-6 we see cellular signaling profiles that tend to promote pathology including cancer, autoimmunity and glucose dysregulation. I see this more like a band or orchestra playing out of tune than too much of one thing vs another thing, but the fact remains folks likely get too much of the short form of N-6 fats. My early solution (and the solution of many other people including Barry Sears, Charles Poliquin and number of other folks) was to front load the system with large amounts of N-3 fats in the form of fish oil to “balance” the intake of N-6 fats. I mentioned a formula in my book for figuring out your fish oil dose and my pals at Whole9 put up a nifty calculator to help you figure out not only how much fish oil you needed overall, but also how damn many capsules that meant depending upon your product of choice.

These recommendations were born several years ago when I was still working for CrossFit, trying to sneak in as much paleo-pseudoscience as I could between polishing the brass of the magical, 40-30-30 Zone. Given the relatively low protein recommendation of the Zone, combined with moderate to low carbohydrate levels, the only thing left to recommend to hard charging athletes was to ramp up fat intake, and what better fat to use than nuts and seeds? Portable, cheap, yummy. Also, 36-DD heavy in linoleic acid. No worries I thought, we’ll just “balance” things out with more fish oil. Well, by looking at performance parameters and blood work it became clear we still had inflammatory issues that were far from optimum. Some digging in the literature and review of the basic metabolic pathways showed that linoleic acid intake tends to squash the anti-inflammatory outputs of our EPA/DHA supplementation. Recommendations were tweaked to get fat from sources low(er) in linoleic acid such as coconut and pastured butter and we observed improvements in performance and various blood parameters including C-reactive protein and fasting insulin levels.

Eventually the Zone was canned and folks were told to get protein and carb intake up to levels that matched activity. Things REALLY improved!

But I was still of the opinion that fairly high dose fish oil was beneficial to folks with significant systemic inflammation and health issues. The recommendation was to take a fairly large amount of fish oil for a few weeks, then titrate that down to a maintenance level. The thinking here was that we could send a large “anti-inflammatory” signal to the system and get the Titanic steering away from the proverbial iceberg. Some folks (smarter than myself like Chris Kresser) had different ideas on this. Chris liked limiting linoleic acid and keeping EPA/DHA to low-ish levels, mainly from food, with perhaps a few grams per day of supplemental fish oil. What I had not initially considered is signaling, be it anti or pro-inflammatory is a cell by cell affair, and this is based largely on the make-up of fatty acids in our cell membranes. In an inflamed, sick, standard American diet model, individuals have a significant overabundance of linoleic acid in their cell membranes. The idea of front loading more EPA/DHA to change the fatty acid profile of our cells is great until you run into the brick-wall of our metabolic machinery. Cell fatty acid turnover cannot be “goosed” from behind like shoving a bungee jumper off a bridge. Fatty acid turnover has a rate limiting step that is not “substrate limited.” Or, in non-geek-speak more fish oil will not make the process go faster. Instead we need to limit the intake of linoleic acid, keep a decent intake of EPA/DHA, but we need not, and in fact should not hammer that dosage, as we will see when we look at oxidative stress and free-radical chemistry.

When we talk about “inflammation” we must consider two basic elements:

1-The immune system (in this case mainly the innate, non-adaptive immune system made up of macrophages, leukocytes and neutrophils…we’ll largely ignore (for today) the adaptive immune response which is involved in autoimmunity)

2-The various cell-signaling components that tell the immune system what to do. Now, almost everyone has heard of oxidative damage, free radicals, antioxidants and the like.

In chemistry we characterize reactions in a number of ways, with most synthetic reactions involving the shuffling of an electron pair between one atom or molecule and another atom or molecule. This is like a banjo-playing square-dance! Fun, safe, predictable. Another type of reaction that we must consider in biological systems, particularly the immune system, is free radical chemistry. In this situation we see a single electron running amuck. This is more akin to a mosh-pit at a punk concert. In the technical parlance free radicals can “fuck-shit-up.”

The innate immune system makes good use of free radicals when battling bacteria, viruses and parasites. If an immune cell comes in contact with something deemed to be a foreign invader the cell will tend to engulf the item, then release a dose of free-radicals that likely will kill the cell, but will also (hopefully) take out the pathogenic interloper in a Kamikaze style mission. As you recall, inflammation involves not only the immune system but also the cellular signaling components such as prostaglandins, leukotriens and a host of other goodies. In the pro-inflamed state the signaling is effectively “high allert.”

The immune cells are ramped up and just looking for a fight. As such, there is a tendency for the immune cells to get a little spastic and attack things they should not. As a consequence, we are subjected to an elevated level of oxidative stress. This is to be expected when fighting a cold or bacteria, but it portends doom when it is an outgrowth of endotoxemia (intestinal permeability, bacterial overgrowth) and elevated systemic inflammation from a diet and lifestyle that is throwing too many of the wrong switches. Now, this is a pretty bad scenario as it is, but if we have large amounts of polyunsaturated fats (like those in fish oil, seed and similar oils) in our system things can go from bad to worse.

Polyunsaturated fats are HIGHLY oxidizable. Linseed oil (refined FLAX oil actually…), if added to paper or rags and left open to the air, can get enough reaction going to combust. This is possible because polyunsaturated fats under go what is called a “chain propagative” reaction. Throw one teensy electron into a cell membrane full of polyunsaturated fats and you can witness a mountain of damage. This is why an individual with significant systemic inflammation would do well to limit polyunsaturated fats (particularly linoleic acid) as they are already experiencing oxidative stress. High levels of polyunsaturated fats in the cell membranes will not help things. This oxidative stress issue pops up in other, unlikely spots that can mask problems which otherwise are ascribed a therapeutic effect. Fish oil supplementation has been associated with decreased blood triglyceride levels. Folks savvy to the underpinning of insulin resistance know that elevated triglycerides are an indicator of insulin resistance, so any intervention that lowers triglycerides should be a good thing. Well…in the digestive process all nutrients must be broken down, passed through the gut lining and eventually make their way to the liver.

Fats are released out of the liver in the form of LDL’s, VLDL’s and the like, but they are tested in the liver for oxidative stress potential. If the package is made up of oxidized lipids (lipid peroxides) the batch is scuttled and the liver attempts to degrade the contents of the sample to prevent damage to the rest of the body. The liver is willing to take this hit as it has a large capacity for regeneration, but as with alcoholic cirrhosis, it does take an ass-kicking. While this chaos ensues in the comfy confines of the liver, our blood triglycerides go down, apparently a good thing, but this is a completely different mechanism of action relative to decreased triglycerides stemming from improved insulin/leptin sensitivity. This is a long-winded way of saying it’s time to revisit our fish-oil recommendations.

So, what should I do?

1-LIMIT linoleic acid!! You’d think after I jumped up and down about his for the past 1500 words that it would be obvious, but I just wanted to make sure we are clear on this. Nuts, seeds, corn, safflower, sunflower and similar seed oils are “no bueno.”

2-Limit linolenic acid form things like flax, hemp, chia etc. I’d prefer you get the bulk of your N-3’s in the ready made forms of EPA/DHA and your N-6’s as aracidonic acid. The conversion of linolenic acid to EPA/DHA is inefficient and overall exposes up to a greater oxidative potential as you must consume MORE total polyunsaturated fats to get the goods. I know there are some folks that recommend these short chain fats. Do whatever you like but this is what makes sense to me.

3-Try to get the bulk of your EFA’s (both N-3 and N-6) from grass fed meat, and perhaps pastured dairy in the form of butter. BUT that’s expensive!! I know Buttercup, I know. Do your best. Sardines, mackerel and similar fish are also great sources.

4-Supplement with 2-4 grams of EPA/DHA heavy oils from fish oil, fermented cod liver oil (god help me…that stuff is NASTY, but Chris Kresser loves the stuff) or vegetarian sourced DHA from algae. The DHA can retro-convert to EPA, so no problems there. Which should it be, 2 or 4 grams? If you are “big” take 4. If you are little, take 2. If you do not know if you are big or little, please disavow all knowledge or the paleo diet and adopt veganism. Please.

At the end of the day I think these recommendation support our best understanding of the science and it seems to reflect clinical findings. It also simplifies things to a great degree. Many a client has balked at the high-dose fish oil that has been part of my and other folks recommendations. I think there are some great supplements for specific purposes (adaptogens, creatine and a few other goodies) but where food is concerned, food seems to be best. Shocker. Similarly, there are not shortcuts to health and wellness, just better information and feedback so we can make better decisions.

About the author

Robb Wolf, author of The Paleo Solution, is a former research biochemist and one of the world’s leading experts in Paleolithic nutrition. Wolf has transformed the lives of tens of thousands of people around the world via his top ranked iTunes podcast and wildly popular seminar series. Read more...